A whole methylome study of ethanol exposure in brain and blood: an exploration of the utility of peripheral blood as proxy tissue for brain in alcohol methylation studies

Background: Recent reviews have highlighted the potential use of blood‐based methylation biomarkers as diagnostic and prognostic tools of current and future alcohol use and addiction. Due to the substantial overlap that often exists between methylation patterns across different tissues, including blood and brain, blood‐based methylation may track methylation changes in brain; however, little work has explored the overlap in alcohol‐related methylation in these tissues.

Methods: To study the effects of alcohol on the brain methylome and identify possible biomarkers of these changes in blood, we performed a methylome‐wide association study in brain and blood from 40 male DBA/2J mice that received either an acute ethanol (EtOH) or saline intraperitoneal injection. To investigate all 22 million CpGs in the mouse genome, we enriched for the methylated genomic fraction using methyl‐CpG binding domain (MBD) protein capture followed by next‐generation sequencing (MBD‐seq). We performed assoc...